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Herbal nutraceuticals: safe and potent therapeutics to battle tumor hypoxia

  • Review – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Growing solid tumors mostly outstrip blood supply and become hypoxic (low oxygen supply). To survive under this pathological milieu, tumors overexpress a potent oncogenic factor, hypoxia-inducible factor-1α (HIF-1α). HIF-1α up-regulate HIF-1 signaling pathways and subsequently activate genes that promote cancer growth even under hypoxia. Also, HIF-1 pathway activation leads to aggressive tumor growth, metastasis, therapy resistance and ultimately poor patient prognosis as evidential by several clinical studies. Hence, targeting HIF-1 pathway is regarded as a promising strategy to treat cancer. To date, several synthetic HIF-1 pathway inhibitors have been developed to treat hypoxic tumors; however, they are clinically ineffective due to off-target effects, low potency and high toxicity. Hence, there is an urgent need to explore safe and promising drugs to combat hypoxic tumors.

Results

This article extensively reviews the therapeutic potential of various herbal nutraceuticals against wide varieties of hypoxic tumors. The inhibitory effects of each herbal nutraceutical on the pathological consequences of HIF-1 signaling pathway and also their ability to improve the response of hypoxic cancer cells to conventional cancer therapies are discussed. Furthermore, we have provided new directions to overcome challenges behind conducting in vivo and preclinical hypoxia research and developing herbal nutraceuticals into pharmaceuticals to treat cancer.

Conclusions

The present review strongly suggests that herbal nutraceuticals are highly effective in combating the oncogenic effects of the HIF-1 pathway in wide varieties of tumors. However, more in vivo studies using zebrafish as a model system and extensive clinical studies in cancer patients with elevated tumor HIF-1α levels are highly warranted to ascertain the effective utilization of herbal nutraceuticals as adjunct/ alternative medicine in clinical practice to treat cancer.

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Acknowledgements

The author’s thanks to Dr. V. Purshoshothaman and Dr. K. Revathi for the critical review of the manuscript. The authors sincerely apologize to any authors whose work was omitted.

Funding

Dr. DN was supported by the Start-up-grant from Meenakshi Academy of Higher Education and Research. Dr. GSK acknowledges CSIR-IICB for seed grant. Dr.JS was supported by ECRA, DST-SERB.

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Authors and Affiliations

  1. Central Research Laboratory, Meenakshi Ammal Dental College, Meenakshi Academy of Higher Education and Research, Maduravoyal, Chennai, Tamilnadu, India

    Devarajan Nalini

  2. Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamilnadu, India

    Jayaraman Selvaraj

  3. Laboratory of Translational Genetics, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, TRUE Campus, CN Block-6, Sector V, Salt Lake, Kolkata, 700 091, India

    Ganesan Senthil Kumar

  4. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Ganesan Senthil Kumar

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  1. Devarajan Nalini
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  2. Jayaraman Selvaraj
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  3. Ganesan Senthil Kumar
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DN and GSK have given an equal contribution in framing review topics, collecting study materials, preparing a manuscript, proofreading, etc. JS has written the terpenoid and isothiocyanate section of the manuscript.

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Correspondence to Ganesan Senthil Kumar.

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Nalini, D., Selvaraj, J. & Kumar, G.S. Herbal nutraceuticals: safe and potent therapeutics to battle tumor hypoxia. J Cancer Res Clin Oncol 146, 1–18 (2020). https://doi.org/10.1007/s00432-019-03068-x

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